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AGO-bound mature miRNAs are oligouridylated by TUTs and subsequently degraded by DIS3L2

  1. Author:
    Yang,Acong [ORCID]
    Shao, Tie-Juan
    Bofill De Ros,Xavier [ORCID]
    Lian, Chuanjiang
    Villanueva, Patricia
    Dai,Lisheng
    Gu,Shuo [ORCID]

  2. Author Address

    RNA Mediated Gene Regulation Section; RNA Biology Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD, 21702, USA., School of Basic Medicine, Zhejiang Chinese Medical University, Hangzhou, 310053, China., State Key Laboratory of Veterinary Biotechnology and Heilongjiang Province Key Laboratory for Laboratory Animal and Comparative Medicine, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, 150069, China., RNA Mediated Gene Regulation Section; RNA Biology Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD, 21702, USA. shuo.gu@nih.gov.,
    1. Year: 2020
    2. Date: Jun 02
    3. Epub Date: 2020 06 02
  2. Journal: Nature communications
    1. 11
    2. 1
    3. Pages: 2765
  4. Type of Article: Article
  5. Article Number: 2765
  6. ISSN: 2041-1723
  1. Abstract:

    MicroRNAs (miRNAs) associated with Argonaute proteins (AGOs) regulate gene expression in mammals. miRNA 3 39; ends are subject to frequent sequence modifications, which have been proposed to affect miRNA stability. However, the underlying mechanism is not well understood. Here, by genetic and biochemical studies as well as deep sequencing analyses, we find that AGO mutations disrupting miRNA 3 39; binding are sufficient to trigger extensive miRNA 3 39; modifications in HEK293T cells and in cancer patients. Comparing these modifications in TUT4, TUT7 and DIS3L2 knockout cells, we find that TUT7 is more robust than TUT4 in oligouridylating mature miRNAs, which in turn leads to their degradation by the DIS3L2 exonuclease. Our findings indicate a decay machinery removing AGO-associated miRNAs with an exposed 3 39; end. A set of endogenous miRNAs including miR-7, miR-222 and miR-769 are targeted by this machinery presumably due to target-directed miRNA degradation.

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External Sources

  1. View Full Text
  2. DOI: 10.1038/s41467-020-16533-w
  3. PMID: 32488030
  4. View record in Web of Science®
  5. WOS: 000543974800021
  6. PII : 10.1038/s41467-020-16533-w

Library Notes

  1. Fiscal Year: FY2019-2020
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